Adenosine Deaminase Activity of Insect-derived Growth Factor Is Essential for Its Growth Factor Activity

Homma, Koichi J.; Tanaka, Yasuhiro; Matsushita, Takefumi; Yokoyama, Kaoru; Matsui, Hitoshi; Natori, Shunji

doi:10.1074/jbc.m105088200

Cited by 27 publications

(28 citation statements)

References 42 publications

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“…A further protein enriched in bacteriocyte samples was ACYPI001365 (#214, 0.11%). Although annotated as "insectderived growth factor," the homolog of this protein has been reported to have adenosine deaminase activity in the fleshfly Sarcophaga peregrine (49), raising the possibility that this protein mediates the transformation of adenosine to inosine.…”

Section: Fig 2 Experimental and Bioinformatics Workflow Of The Protmentioning

confidence: 99%

Large-Scale Label-Free Quantitative Proteomics of the Pea aphid-Buchnera Symbiosis

Poliakov

Russell

Ponnala

et al. 2011

Molecular & Cellular Proteomics

133

166

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Section: Fig 2 Experimental and Bioinformatics Workflow Of The Protmentioning

confidence: 99%

Large-Scale Label-Free Quantitative Proteomics of the Pea aphid-Buchnera Symbiosis

Poliakov

Russell

Ponnala

et al. 2011

Molecular & Cellular Proteomics

133

166

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“…The ADGF/ADA2 family proteins (3,14,15) were first described as growth factors in insects (16,17) and later were found to possess the ADA activity, which was shown to be essential for the growth factor activity (3,18,19). The physiological role is best described for the Drosophila homologue, ADGF-A (3,20).…”

mentioning

confidence: 98%

“…As we also found that ADA2 can bind to and modulate the affinity of ADRs, we hypothesized that the ADA2 binding to T cells is mediated by ADRs or an ADR-proteoglycan complex. Previously, the binding to the cell surface via unknown receptors was found for insects (17,18) and proposed for amphibian homologues (19), suggesting that this might be a common signaling mechanism for ADGF/ADA2 proteins that is complementary to or cooperating with the signaling via the enzymatic activity.…”

mentioning

confidence: 99%

Structural Basis for the Growth Factor Activity of Human Adenosine Deaminase ADA2

Zavialov

Spillmann

et al. 2010

Journal of Biological Chemistry

112

124

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Two distinct adenosine deaminases, ADA1 and ADA2, are found in humans. ADA1 has an important role in lymphocyte function and inherited mutations in ADA1 result in severe combined immunodeficiency. The recently isolated ADA2 belongs to the novel family of adenosine deaminase growth factors (ADGFs), which play an important role in tissue development. The crystal structures of ADA2 and ADA2 bound to a transition state analogue presented here reveal the structural basis of the catalytic/signaling activity of ADGF/ADA2 proteins. In addition to the catalytic domain, the structures discovered two ADGF/ADA2-specific domains of novel folds that mediate the protein dimerization and binding to the cell surface receptors. This complex architecture is in sharp contrast with that of monomeric single domain ADA1. An extensive glycosylation and the presence of a conserved disulfide bond and a signal peptide in ADA2 strongly suggest that ADA2, in contrast to ADA1, is specifically designed to act in the extracellular environment. The comparison of catalytic sites of ADA2 and ADA1 demonstrates large differences in the arrangement of the substratebinding pockets. These structural differences explain the substrate and inhibitor specificity of adenosine deaminases and provide the basis for a rational design of ADA2-targeting drugs to modulate the immune system responses in pathophysiological conditions.

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“…Next, we examined the growth factor activities of Xl_ CECR1-1 and Xl_CECR1-2 in NIH-Sape-4 cells, as these cells are sensitive to various invertebrate ADGFs (1,3,10,11,15). Although both Xl_CECR1-1 and Xl_CECR1-2 showed growth factor activity, Xl_CECR1-1 displayed activity at lower concentrations than Xl_CECR1-2 ( Fig.…”

Section: Identification and Characterization Of X Laevis Cecr1 Cdnas-mentioning

confidence: 99%

“…ADA activity has been reported for some ADGF/CECRs (9 -14), including IDGF (3), where the K m , V max , and k cat values are comparable with those of mammalian cytoplasmic ADAs (21). As IDGF was originally identified as a growth factor in an embryonic cell line (1) and ADA activity was shown to be indispensable for growth factor activity (3), it is plausible that the ADGF/CECR1 family plays a role in cell proliferation during morphogenesis and organogenesis via its ADA activity.…”

mentioning

confidence: 99%

The Extracellular Adenosine Deaminase Growth Factor, ADGF/CECR1, Plays a Role in Xenopus Embryogenesis via the Adenosine/P1 Receptor

Iijima

Kunieda

Yamaguchi

et al. 2008

Journal of Biological Chemistry

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Adenosine deaminase-related growth factors (ADGF), also known as CECR1 in vertebrates, are a novel family of growth factors with sequence similarity to classical cellular adenosine deaminase. Although genes for ADGF/CECR1 have been identified in both invertebrates as well as vertebrates, their in vivo functions in vertebrates remain unknown. We isolated cDNA clones for two cerc 1s from Xenopus laevis. Both recombinant Xenopus CECR1s exhibited adenosine deaminase and growth factor activity, and the adenosine deaminase activity was found to be indispensable for growth factor activity. The Xenopus cerc 1s are expressed in the somites, pronephros, eyes, cement gland, neural tube, and neural floor plate of the embryos. Knock-down of these two genes using morpholino oligonucleotides caused a reduction in the body size and abnormalities of the body axis in the Xenopus embryos, accompanied by selective changes in the expression of developmental marker genes. Injection of adenosine, agonists for adenosine/P1 receptors, or adenosine deaminase inhibitor into late gastrula archenteron embryos resulted in developmental defects similar to those caused by morpholino oligonucleotide injection. These results show, for the first time, the involvement of CECR1s via the adenosine/P1 receptors in vertebrate embryogenesis via regulation of extracellular adenosine concentrations.Growth factors play important roles in morphogenesis and organogenesis in various animal species. Of these, the adenosine deaminase-related growth factor (ADGF) 3 family is a novel group of growth factors with sequence similarity to classical adenosine deaminase (ADA) in their carboxyl-terminal regions (1-3). Classical ADA is a cytoplasmic enzyme that catalyzes the deamination of adenosine and 2Ј-deoxyadenosine to inosine and 2Ј-deoxyinosine, respectively (4), and has a wide phylogenetic distribution (5). ADA is involved in purine metabolism and plays an indispensable role in the upkeep of a competent immune system in mammals (6). In contrast, ADGFs are comprised of secretory or transmembrane-type ADGFs (1, 2, 7, 8), with some having growth factor-like activities (3, 9 -14).Insect-derived growth factor (IDGF), the first ADGF to be cloned, is a secretory ADGF purified from the conditioned medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina (flesh fly) (1). IDGF stimulates the growth of NIHSape-4 cells with a specific activity comparable with mammalian growth factors. Site-directed mutagenesis has demonstrated that the ADA activity of IDGF is essential for its growth factor activity (3, 15). So far, ADGF families have been reported in various invertebrates. In Drosophila melanogaster (fruit fly), Male-specific IDGF was identified as a transmembrane-type ADGF and is suggested to participate in spermatogenesis (7). Recently, six ADGFs have been identified in Drosophila, one of which (Adgf-A2) encodes Male-specific IDGF (8, 16). In addition, ADGF families have been identified in other fruit flies, sand flies, sea slugs, tsetse flies, mosquitoes, fu...

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Adenosine Deaminase Activity of Insect-derived Growth Factor Is Essential for Its Growth Factor Activity

Cited by 27 publications

References 42 publications

Large-Scale Label-Free Quantitative Proteomics of the Pea aphid-Buchnera Symbiosis

Large-Scale Label-Free Quantitative Proteomics of the Pea aphid-Buchnera Symbiosis

Structural Basis for the Growth Factor Activity of Human Adenosine Deaminase ADA2

The Extracellular Adenosine Deaminase Growth Factor, ADGF/CECR1, Plays a Role in Xenopus Embryogenesis via the Adenosine/P1 Receptor

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